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Rare Pediatric Epilepsies in Adult Neurology: Sharpening Your Specter of Suspicion

  • Authors: Anup D. Patel, MD; Elizabeth A. Thiele, MD, PhD
  • CME / ABIM MOC Released: 10/17/2022
  • Valid for credit through: 10/17/2023
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Target Audience and Goal Statement

This activity is intended for neurologists, primary care physicians, pediatricians, and other clinicians involved in the care of patients with rare neurological diseases.

The goal of this activity is for learners to be better able to identify a missed diagnosis of Lennox-Gastaut syndrome (LGS), Dravet syndrome (DS), or tuberous sclerosis complex (TSC) in the adult neurology setting, and what such a diagnosis indicates for the selection of anti-seizure medications.

Upon completion of this activity, participants will:

  • Have increased knowledge regarding the
    • Diagnostic criteria for rare pediatric-onset epilepsies
  • Have greater competence related to
    • Accurately diagnosing a rare pediatric-onset epilepsy in an adult patient
    • Selecting an appropriate medication for the management of seizures in adult patients with rare pediatric-onset epilepsies


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  • Anup D. Patel, MD

    Associate Professor, Clinical Pediatrics and Neurology
    The Ohio State University College of Medicine
    Section Chief, Pediatric Neurology
    Nationwide Children's Hospital
    Columbus, Ohio


    Anup D. Patel, MD, has the following relevant financial relationships:
    Consultant or advisor for: Jazz Pharmaceuticals; Neurelis
    Research funding from: Encoded; Greenwich Biosciences; Stoke Therapeutics


  • Elizabeth A. Thiele, MD, PhD

    Professor of Neurology
    Harvard Medical School
    Director, Pediatric Epilepsy Program
    Director, Carol and James Herscot Center for Tuberous Sclerosis Complex
    Massachusetts General Hospital
    Boston, Massachusetts


    Elizabeth A. Thiele, MD, PhD, has the following relevant financial relationships:
    Consultant or advisor for: Aditum; Azurity; BridgeBio; GW Pharmaceuticals; Jazz Pharmaceuticals; LivaNova; Marinus; Nobelpharma; Radius Health; Stoke Therapeutics; Zogenix
    Research funding from: GW Pharmaceuticals; Jazz Pharmaceuticals; Stoke Therapeutics; Zogenix
    Contracted researcher for: GW Pharmaceuticals; Jazz Pharmaceuticals; Zogenix


  • Walid Amara, MD

    Medical Education Director, WebMD Global, LLC


    Walid Amara, MD, has no relevant financial relationships.

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  • Stephanie Corder, ND, RN, CHCP

    Associate Director, Accreditation and Compliance, Medscape, LLC


    Stephanie Corder, ND, RN, CHCP, has no relevant financial relationships.

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This activity has been peer reviewed and the reviewer has no relevant financial relationships.

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Rare Pediatric Epilepsies in Adult Neurology: Sharpening Your Specter of Suspicion

Authors: Anup D. Patel, MD; Elizabeth A. Thiele, MD, PhDFaculty and Disclosures

CME / ABIM MOC Released: 10/17/2022

Valid for credit through: 10/17/2023


Activity Transcript

Anup Patel, MD: Hello, everyone. Thank you for joining us today for Rare Pediatric Epilepsies in Adult Neurology, Sharpening Your Specter of Suspicion. Joining me today is my colleague and friend, Elizabeth Thiele. She's a Professor of Neurology at the Harvard Medical School, Director of the Pediatric Epilepsy Program, Director of the Carol and James Herscot Center for Tuberous Sclerosis Complex, Massachusetts General Hospital in Boston, Massachusetts. Welcome, Elizabeth.

Elizabeth Thiele, MD, PhD: Thanks, Anup.

Dr Patel: Here's our agenda for today's webinar. We're going to have an introduction and then go over some features and epidemiology of Dravet syndrome (DS), Lennox-Gastaut (LGS), and tuberous sclerosis complex (TSC), and really focus on the misdiagnosis and potential pitfalls as it results. We're going to go through a couple of cases, bring us all back together and summarize.

So let me start off by talking about rare epilepsies in children, and really what's important is we now know that these syndromes and children living with these syndromes live well into their adult years. So it's really going to be important for both pediatric and adult providers to recognize signs, symptoms, and also the treatment as it relates to these syndromes when these children grow into being adults.

The other thing to remind us about is that a lot of times adults will present to epilepsy centers, and they may have an unknown reason for their epilepsy, and that may be because of a genetic reason. And so it's something to keep in mind that even then, the diagnostic odyssey may not have ended.

So let's talk a little bit about epidemiology. Well, many of you may be familiar with Lennox-Gastaut syndrome, but in case you're not, I'd like to cover some of the basic aspects of that. One of the most important features of Lennox-Gastaut is the seizure type, and remind you that multiple seizures need to be present, along with a cognitive impairment, either intellectual regression, slowing, or some behavioral issues. And then you can see this characteristic EEG pattern of what we call slow, spike, and wave, and you can also see paroxysmal fast activity, and that's going to be usually seen during non-REM sleep.

One most important point about EEG features as it relates to Lennox-Gastaut syndrome, know that they will change over time, and you may not have that classic triad well into the course, especially once they get into the adolescent and adult years.

So, when we look at the criteria, let's break that down specifically and understand some more of the statistics. So when we talk about the different types of seizures, again, the most prevalent type is tonic seizures upon awakening. But remind you that 1% to 10% of all child epilepsies and 7% of children with intellectual disabilities have Lennox Gastaut syndrome, so it can and is a very common presentation.

Some other stats to familiarize yourself with is this incidence of 0.1 to 0.28 per 1000 life births have Lennox-Gastaut syndrome, and it's approximately 2 per 100,000 per year. And like I said earlier with the 7%, 7% of children who have intellectual disability have Lennox-Gastaut syndrome.

So what about the lack of diagnosis? Well, there's a great study out of Colorado Children's that looked at children who presented with infantile spasms and then went on to look at what their care entailed. Remind you that many of the children who have infantile spasms can go on and develop Lennox-Gastaut syndrome. And you can see that in this study, many of the children who actually had infantile spasms or history, 36% of those met criteria for Lennox-Gastaut syndrome. However, a fair number were undiagnosed.

What about Dravet syndrome? A little familiarity with Dravet syndrome, most commonly related to a genetic variation in the SCN1A gene, usually a presentation with febrile status epilepticus at normal development at onset, but then often the delays will start to occur by age 12 months. And the incidence is about 1 in 15,500 births.

So what about a late diagnosis of Dravet syndrome? So there was a study in England that looked at adult patients with what was considered to be complex epilepsy with an unknown etiology. So in this study, they looked at 1,078 patients, and when they tested them with genetic testing, they found that 8 had a pathogenic variation in the SCN1A gene and met criteria for Dravet syndrome.

When they look back at the history of these patients, they realized that all of them had a history of febrile illness that then triggered seizures and a lot of history of myoclonic seizures, which is a very common seizure type seen in children and adults with Dravet syndrome. They also noted that their median age of seizure onset was at 6 months. And what was most fascinating in this study is the median number of previous treatment with anti-seizure medicines was 11, and that all of these patients were treated with what traditionally would be avoided in patients with Dravet syndrome, what we call sodium channel mechanism of action. And none of those patients, when you look at their current seizure treatment or anti-seizure treatment were treated with traditionally FDA-approved or approved treatments for this condition.

So now, I'm going to pass it on to Dr Thiele, but before I do, I didn't know if there's anything else Dr Thiele would like to mention as it relates to the misdiagnosis or late diagnosis of Lennox-Gastaut syndrome or with Dravet syndrome.

Dr Thiele: I think just that your point is very true. I think especially this most specific diagnosis is really, really necessary and becoming more so as we move closer to precision medicine. With the FDA specific approval of medications for these disorders, it's difficult to get access to the treatment if you don't know that you have the diagnosis. So I would agree with you. And thanks for giving me the opportunity to talk about tuberous sclerosis.

As you know, it's been a large focus of my career. And over the past 10, 20 years, we've learned a lot about TSC, both with regard to genetics as well as the clinical manifestations and treatment. As we all know, TSC is an autosomal dominant disorder, but about two-thirds of patients who are diagnosed have TSC as a result of a spontaneous mutation, meaning no family history. We also know that in patients who meet clinical criteria for TSC, we can identify a disease causing or pathogenic mutation in either the TSC1 or TSC2 gene. We also know that the TSC2 are more common being found almost 6 times as often as TSC1, and overall, TSC2 mutations also carry a more severe phenotype. In those that we cannot identify a mutation or no mutation identified or NMI, we now believe that many of those were due to low level mosaicism of either TSC1 or TSC2 gene.

We've also learned in 20 years that TSC1 and TSC2, we know a lot about their function now, and we know that they inhibit mTORC, and therefore pathologic variant mutation results in upregulation of mTORC activity, which leads to abnormalities in cell regulation and control and the various manifestations that we see in patients with TSC. And as we said, the TSC2 mutation often is associated with a more severe phenotype, but not always. Some of my most mildly affected patients have a TSC1 mutation, and more severely, mutations of TSC1, but overall, TSC2 is a more severe phenotype.

TSC can affect almost every organ system, which is one of the things that is really fascinating about the disorder, and the brain and the skin are the 2 most affected organ systems, both affected in about 90% of people with TSC. We also know that in patients with TSC, there's a very wide phenotypic variability, and including within family sharing the same mutation, where one family member may be mildly affected, another family member more severely affected. And TSC is not that rare. It's now thought to affect about 1 in 6000 live births, meaning that about 2 million people worldwide are living with TSC and about 50,000 in the United States.

As I said, the brain and the skin are the most affected organ features. And in the brain, as we'll talk about, epilepsy is quite common. And the majority of patients also have subependymal nodules, one of the anatomic features, and about 10% to 15% of children with TSC will develop subependymal giant cell astrocytomas.

Over the past 10, 15 years, there's been increasing awareness and study into the mental health aspects of TSC or the TSC-associated neuropsychiatric disorders, and we'll also talk about those a little later. We know that about 50% of individuals have some degree of intellectual disability, and up to 40% have autism, so significant brain involvement in TSC, as well as the other possible organ manifestations.

Epilepsy, as you said, is common and is actually the most common symptom of TSC, affecting up to 90% of patients. And typically, onset is in the first year of life. About 70% of patients with tuberous sclerosis will have seizures during the first year of life. And we know that the earlier the onset and the more difficult to treat the epilepsy is, there is a greater risk of delayed psychomotor development, abnormal speech, and autism.

And kind of the graft on the brightest work we did several years ago, we were looking at our TSC population. As you can see, the majority of patients have onset of seizures the first year of life in childhood, but seizure onset in adolescents and adulthood is not rare. About a third of patients with TSC will develop infantile spasms, making it one of the leading etiologies of infantile spasms. And interestingly, of those who develop infantile spasms in TSC, one-third will have a normal cognitive outcome. And we also know that in TSC, children with infantile spasms, vigabatrin is particularly effective in treating seizures for them.

We also know that in tuberous sclerosis complex, epilepsy is not uncommon and occurs up into two-thirds of patients, so about double the rate of refractory epilepsies in the general epilepsy population. But importantly, we also know that some patients do experience long-term remission, including many who are able to come off of medication. And this is important, because it's not uncommon for me to meet a family or a patient living with TSC, who've been told that they'll need to be on seizure medications all of their lives. That is not necessarily true.

Looking at the age of diagnosis of TSC, you can see in this review again, the diagnosis usually does occur in childhood, early infancy, often due to seizures, but is just with Dravet syndrome and Lennox-Gastaut and tuberous sclerosis complex, the diagnosis is often delayed or missed. And we looked at this in our patient population years ago, and we found that, again, the age of TSC diagnosis was from birth to 73. The oldest person I've diagnosed was 73 years of age, even though there were missed symptoms for him as well. And the average age of our patients who were diagnosed was about 7.5 years. The majority were diagnosed less than 10 years of age, but as we said before, diagnosis during adolescence or adulthood was not uncommon.

And in our population, I was honestly surprised to find that 39% had missed symptoms or signs of TSC that could have led to an earlier diagnosis, which could have had impact on their disease course.And I was really disappointed and surprised to learn that seizures, including infantile spasms, as well as dermatologic features, were the most common missed signs. We've seen many of our patients with TSC that were diagnosed with epilepsy, often decades before they were diagnosed with TSC. So often missed signs.

As we know, also TSC is a clinical diagnosis, even though we do have genetic testing and identifying a pathogenic variant does play a role. We still diagnose it according to major clinical criteria and minor clinical criteria, the major being things that are seen very frequently in TSC and not so frequently in the general population, and the minor criteria are things that we see a lot in TS that are also seen in the general population.

To be diagnosed with definite TSC, a patient needs to have major features or 1 major feature and 2 minor features. And we also do consider the diagnosis of possible TSC, since many of these manifestations can occur at different times during an individual's life. It's important to monitor patients with possible TSC as well, and possible TSC is diagnosed with either 1 major or 2 minor features. And I'll turn it back to you, Anup, for your case.

Dr Patel: Thank you. Thank you for that great summary of TSC. I think one point that's really important is the fact that some patients with TSC can, in fact, be weaned off their anti-seizure medicines, which traditionally you may not see with Dravet or Lennox-Gastaut syndrome.

So let's go through the case portion of our webinar today. The first case we're going to talk about is a 23-year-old, and basically I want to go through some of the scenarios as it relates to this not-so-fictional case. So, this is a 23-year-old woman, who presents to an epilepsy center after being established for care after transition to a group home. When you look at the person's history, she had febrile seizure status epilepticus at 6 months of age, that recurred resulting in 3 admissions within 2 months of the initial seizure. She was also noted to have slow development starting at age 1. She started to develop myoclonic seizures about one-and-a-half years, and then continued to have generalized tonic-clonic seizures.

Now, she has significant delays in her development, an hypotonia, and what's noted to be a crouched gait. When you look at some of her testing features, her brain MRI was reported as normal. Her EEG showed generalized spike-wave discharges. No genetic testing was performed in this situation. Treatments that were tried and failed, levetiracetam, oxcarbazepines, niacinamide, topiramate, and lamotrigine. When she presents to the adult center, she is on lacosamide and levetiracetam.

So when we look at suspected diagnosis, a lot of this is this diagnosis of Dravet. And as we talked about during our previous portion of this, this can be a regular scenario where the person is potentially missed and genetic testing was not obtained. So with that in mind, where we would go and how we adjusted this case? There's no right answer, and in a second, I'll bring Dr Thiele back on, because I'd like to hear her thoughts on some of this.

But basically in this scenario, we would want to potentially introduce clobazam as a treatment, knowing that it has some efficacy in Dravet syndrome. Perhaps ween her off of lacosamide due to the sodium channel properties of this medication. I still think it's worth getting a genetic testing in this situation, a potential gene panel, to confirm the diagnosis. Even though Dravet can and is still a clinical diagnosis, then what you can consider is stiripentol, cannabidiol, fenfluramine, or valproic acid. The reason why you would potentially shy away from valproic acid is the nature of this being a female patient and knowing what we see with women in side effects, as it relates to valproic acid.

Before I move on to the next slide, I would like to bring Dr Thiele back and see any thoughts on the case or any kind thoughts on the initial diagnosis plan before we move on to consider some other treatments as it relates to Dravet?

Dr Thiele: No, I agree with you, Anup, and I often have the discussion with my adult epilepsy colleagues that oftentimes when they meet these patients that they may know had childhood onset epilepsy, the early history is not often available, and especially for those individuals living in group homes, et cetera. So that's why I'm really happy that the use and utilization of gene panels are becoming more popular and actually reimbursed by payers in the adult world. Because as we said earlier, now that we do have these FDA-approved treatments, which I do think are game changers for individuals living with Dravet, at least as I've seen in my own patient population, again, to have access to those, oftentimes you need to have the specific diagnosis.

So, it's great if the individuals are still with their family members, who remember the history, their first seizure, et cetera. But I think that the gene panel can be very, very helpful, I think, for Dravet, and it will become only increasingly important for other genetic epilepsies.

Dr Patel: Yeah, I couldn't agree more. And I think the other thing to add with that, it may also make treatment choices a little easier from an authorization standpoint. Insurance may balk or fight back on some of the treatments that you would want to recommend. And when we talk about the FDA-approved treatments, specifically for Dravet syndrome, there are medications that now are FDA-approved here in the United States. Cannabidiol was technically the first FDA-approved treatment, although stiripentol had been used clinically for several years in the population based on some European studies. It became the second FDA-approved medication or anti-seizure treatment.

Another one that's more recent or new is fenfluramine, and I think the important point I want to make on these treatments as it relates to Dravet syndrome is that the fact that these are still treatments for the adult population, and so there's nothing that necessarily changes. Now, you may adjust your treatment protocols based on other comorbidities or the gender, like I mentioned, but it's important to know these are still available. Valproic acid, topiramate, benzodiazepines, and ketogenic diet have also been shown in the literature to have some success. And most importantly, like I mentioned earlier, you'd want to avoid sodium channel medications. In this case, the person was on lacosamide, and perhaps that was not the best treatment.

Don't forget about your rescue plans. It's really important that our adult colleagues think of rescue plans as it relates to children, who now become adults and are under their care, specifically as it relates to what we would consider to be rare epilepsy syndromes. And the bigger things to think about is if medicines are not effective or well tolerated, make sure you change and make sure you find that right combination.

So some of the other questions I wanted to pose, we talked about the need and importance of genetic testing, but Dr Thiele, I'm going to bring you back real quick before we move on to your case. What is your first line treatment for an adult with Dravet syndrome, and is that different from a child that you would see with Dravet?

Dr Thiele: So I think my management of Dravet patients is very similar and in accordance with the recently published international guidelines for the treatment. I've been wicked excited. We have these new FDA-approved medications. I think most of us would still use valproate or clobazam as first line. I'm also a big zealot for dietary therapy and have found it to be effective and increasing use of the diet in adults. But I think that if the patients had already been on a few of those treatments and still having seizures, I would absolutely move to fenfluramine, cannabidiol, because I've seen them be very effective, and I think that overall their tolerability profile is really good.

Dr Patel: And real quick, I wanted to ask a quick question about surgery options. Do you consider surgical options for people with Dravet syndrome?

Dr Thiele: So, I do not, and I know, especially before the identification of the gene and the identification of Dravet syndrome, I think some of these patients did have epilepsy surgery due to the highly refractory nature of their seizures. I don't know a literature on that, Anup. I know of some Dravet patients who have had surgery that was not effective, either corpus callosotomy or certain neuromodulation as that type of surgery plays a role. But I don't really know about the overall experience of epilepsy surgery, but I don't really consider it a top, even necessarily a good option for these patients.

Dr Patel: Thank you. And real quick on Lennox-Gastaut before I turn it back over to Dr Thiele's cases, very similarly, there are treatments and there are FDA-approved treatments for Lennox-Gastaut syndrome. I know we didn't have time in this webinar to cover a case of an adult with Lennox-Gastaut syndrome, but again, a lot of the same principles apply. And in front of you, you see a list of what we have and what we know is FDA-approved treatments in Lennox-Gastaut syndrome, and specifically some of the newer treatments are listed at the bottom here. Specifically, I think it's important that treatments can overlap as it relates to the 2 syndromes, but in this situation, sodium channel drugs are not contraindicated per se, but may not be your first choices.

So, there's a nice paper that was published more recently with an expert consensus on approaching adults for treatment with anti-seizure medications for Lennox-Gastaut syndrome. And this is what the consensus paper and the authors put together, as far as tier one being valproate, clobazam, lamotrigine or safinamide, topiramate, cannabidiol. Then tier 2 would be considered levetiracetam, perampanel, or zonisamide, with tier 3 being felbamate, lacosamide, brivaracetam, and cenobamate. They also said you should consider non-pharmacological treatments. In this case, I think there are surgical options, like the corpus callosotomy. Also neuromodulation, which we're learning more about, as Dr Thiele mentioned earlier for Dravet.

So? I'm going to go ahead and move on, and I want to just summarize some quick things before we go over to case 2, is the importance of early diagnosis in Dravet syndrome, potentially using some newer treatments early that are FDA-approved, so getting the right medicine to the right patient. With LGS, there's lots of choices. None are necessarily transformative, but it's basically about efficacy and mitigating side effects. And then just remember in general, when we talk about the developmental epileptic encephalopathies, it's important that we choose treatments based on seizure types, etiology, if known, and look out for more information that may be coming as far as potential options for them.

So, with that, I would like to turn it over to Dr Thiele to go over case number 2.

Dr Thiele: Thanks a lot, Anup. So my case is a patient with tuberous sclerosis complex, Mark, and he first presented to a neurologist at the age of 18 years, as he had developed some paroxysmal episodes, very stereotyped, during which he felt as if he was continuously falling and described as having a sudden sensation of feeling as if he would fall and would need to grab onto the nearest object to stabilize himself, and these lasted approximately 3 to 5 seconds.

When he was describing one of the episodes to me, he said he almost felt the feeling of going down a steep rollercoaster. Initially, these episodes were very infrequent, but they increased where they were near continuous and very significantly impacting his quality of life. And during the episodes, he did not believe that he had any alteration in consciousness but was very aware of having this feeling.

As he was paroxysmal and very stereotyped, the neurologist did get an EEG, and the EEG was mildly abnormal due to increased focal slowing in the left hemisphere. It was seen with hyperventilation, but no epileptic form activity was seen. And due to the episodes and the focal slowing in the left hemisphere, he had an MRI scan, and the MRI scan did show multiple areas of T2 hyperintensity signal abnormality involving the white matter, and the differential in the report included ADM, vasculitis, or multiple sclerosis.

Mark also had psychiatric symptoms, had significant anxiety, and possible panic attacks and also had a family history of anxiety, but there was no family history of epilepsy or other neurologic disorders. And academically, Mark was doing very well and lived at that time with his parents and his sister.

So as these events were very stereotyped, it was really uncertain, looking through the prior neurology notes, were these related to the anxiety and a type of panic attack this sensation, or could they be focal seizures? So he was started on phenobarbital and was then transitioned to carbamazepine, because he continued to have these episodes while on phenobarbital. After transitioning to carbamazepine, he experienced a significant decrease in the frequency of episodes, although he did continue to have these occasionally during intercurrent illness or significant stress. So at that time, I think both Mark and his neurologic treatment team thought that they were most likely focal seizures, having responded to medication and still being seen when typical seizure triggers would be associated with them.

Then years later, Mark became a father, and he had a daughter. And when his daughter was 5.5 months old, she developed paroxysmal episodes and was diagnosed with focal-onset seizures. On exam at the time of her diagnosis, it was noted that she had multiple hypopigmented macules. And an MRI was performed, which identified cortical tumors as well as subependymal nodules. So based on that MRI, she met criteria for tuberous sclerosis complex, even without including the hypopigmented macules, it was all 3 major criteria for the diagnosis. And she had a gene panel that was done, which identified a mutation in TSC2 gene.

So going back, then, to Mark, since he had a daughter with TSC, and when a child is diagnosed with tuberous sclerosis complex, it is recommended that both parents also be evaluated, either through genetic testing or through clinical examination. So Mark was evaluated, and Mark was found to have facial angiofibroma and 1 perianal fibroma. So again, major criteria.

As part of the complete clinical evaluation, Mark also had an abdominal MRI, which identified a 2-centimeter solid lesion in the left kidney, and biopsy of that was consistent with renal cell carcinoma. So it was really fortunate for Mark that his daughter was diagnosed with TSC, leading to his diagnosis and identification of renal cell carcinoma, which we know can be seen in individuals with TSC, particularly younger individuals. Mark then was diagnosed with TSC after meeting the clinical criteria and was found to share the same TSC mutation as his daughter.

So for Mark, a misdiagnosis, and so why? He had a history of significant anxiety and also likely panic attacks, and were the paroxysmal episodes possible panic attacks? There was no reported alteration of consciousness. The EEG did not have significant upfront features, although none of the episodes were captured on EEG. And as we said before, the episodes improved after he started seizure medications.

I think a key in maybe the missed diagnosis was that Mark had normal cognition, and I think a lot of our colleagues still expect people with tuberous sclerosis to have intellectual disability. So it's really important to remember that 50% of individuals living with TSC have normal cognition. And Mark, as we said earlier, did very well academically, but his MRI was not normal. And if you go back and read the T2 hyperintensity, in addition to possibly being consistent with ADM, vasculitis, and multiple sclerosis, those findings could also be consistent with tuberous sclerosis complex.

So again, very important to put MRI features into clinical context, because his clinical context was definitely much more suggestive of seizure than of those other conditions. And anxiety. Although mark had a family history of anxiety, we know that anxiety is very, very common in individuals with TSC and Obsessive-compulsive disorder (OCD) type anxiety. And as we said before, now, there's such appreciation for this that we have the acronym TAND.

And what about the skin findings? Again, important, and I think every time I talk to medical students about how you evaluate children with epilepsy, it's do a thorough general exam, particularly the skin exam, because not only tuberous sclerosis, but some of our other genetic epilepsies are associated with skin findings. So, Mark likely could have been diagnosed much earlier had he had a close skin exam, looking for the findings.

And this is just to highlight this slide, these TSC-associated neuropsychiatric disorders, because they are present in almost 100% of individuals with TSC and are often misdiagnosed, undiagnosed, and definitely undertreated. So the TAND is broken down into behavioral aspects in TSC, psychiatric, again frequently seeing children or adults with autism. Anxiety, again, very, very common. Intellectual is, again, 50% of individuals will have some degree of intellectual disability, academic, psychosocial, and neuropsychological. So now, the care of individuals with TSC is focused really on addressing, identifying, and treating the various aspects of TAND.

To turn then to infantile spasms, which we said occurs in a third of babies with TSC, first line therapy, definitely, unarguably vigabatrin, and that's often used up to 24 months of age due the concern of recurrence of seizures or spasms, and that's really to maximize seizure control and/or prevention. And actually in the world of TS, we are at a phase where we are trying to prevent seizures. If your child has TSC, can we follow their EEG and initiate vigabatrin prior to seizure onset?

Second line therapy, since vigabatrin is not always completely effective, would be hormonal treatments, including ACTH or prednisone. And then third line anti-seizure medications in the management of spasms would include topiramate, valproate, or definitely dietary therapy, which we and others have shown can be very effective in managing not only spasms but focal seizures in TSC. And then patients with TSC definitely should be considering epilepsy surgery, either if they have refractory spasms or refractory focal seizures, because we know that epilepsy in TSC is definitely focal in etiology.

Anup, that case is really instructive for me. I have seen plenty of patients who are diagnosed with TS after their child is or diagnosed with TS down the road. And again, not only for the neurologic aspects of TSC, but for the other, particularly renal, aspects of TSC, I really believe it's important if an individual with tuberous sclerosis has tuberous sclerosis, that they know they have it.

Dr Patel: Yeah. And I appreciate that. I think what's important is this multidisciplinary approach is really key. And I think that's going to be true of any rare epilepsy syndrome, but even more importantly with TSC.

I really want to highlight some take-home messages for the audience. Children with treatment-resistant focal seizures often require multiple treatments for their epilepsy. These children often remain resistant to treatment, and other considerations like surgery or diet therapy are important. It's also really important to familiarize yourself with some of the newer treatments and know that potentially they're going to be very beneficial, even well beyond or many years into the diagnosis. Don't forget about the comorbidities and getting the right help with that. And again, the multidisciplinary approach of all the needs that go into treating epilepsy and, more importantly, optimizing the care of people with epilepsy.

So with that, I think we will conclude our session. I would like to say thank you for participating in this activity. Please do not forget to answer your poll questions. And I would also like to thank Dr Thiele. I learn always a ton from when I do anything with her, and she is a dear friend and colleague, and so it's always wonderful to do any event with her. So with that, I will conclude our session and thank you for participating in this Medscape live event. Take care, everybody.

This transcript has not been copyedited.

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